Many alkaloids, and particularly those compounds having an azabicyclo ring structure, are useful as physiologically active substances. In particular, optically active 3-quinuclidinol derivatives are important compounds as production raw materials of pharmaceuticals.
A conventionally known process for industrial production of optically active 3-quinuclidinol consists of direct asymmetric hydrogenation of 3-quinuclidinone using inexpensive hydrogen gas for the hydrogen source in the presence of an asymmetric hydrogenation catalyst (Patent Documents 1 to 4).
In this production process, an optically active transition metal complex having an optically active diphosphine and 1,2-diamine as ligands is used for the asymmetric hydrogenation catalyst.
For example, the optically active transition metal complex described in Patent Document 1 has a bisbinaphthyl compound derivative having an asymmetric axis for the optically active diphosphine ligand, that described in Patent Document 2 has a bisbiphenyl compound derivative having an asymmetric axis for the optically active diphosphine ligand, that described in Patent Document 3 has a ferrocene compound derivative having an optically active group in a side chain thereof for the optically active diphosphine ligand, and that described in Patent Document 4 has an alkane compound derivative having an asymmetric carbon for the optically active diphosphine ligand. In addition, the optically active transition metal complexes of all of these patent, documents have optically active or racemic 1,2-diamine compounds as diamine ligands. Hydrogenation reactions are allowed to proceed under mild conditions by all of the asymmetric hydrogenation catalysts described in these publications.
However, the processes described in Patent Documents 1 and 3 have low enantiomeric excess for the resulting quinuclidinol and low catalyst efficiency, the process described in Patent Document 2 has low catalyst efficiency, and the process described in Patent Document 4 has low enantiomeric excess for the resulting quinuclidinol.
Thus, there is a desire for the development of a process that enables direct asymmetric hydrogenation of 3-quinuclidinone having high attainment rates for both enantiomeric excess and catalyst efficiency.                [Patent Document 1] Japanese Unexamined Patent Application, First Publication No. 2003-277380        [Patent Document 2] Japanese Unexamined Patent Application, First Publication No. 2005-306804        [Patent Document 3] Japanese Unexamined Patent Application, First Publication No. 2004-292434        [Patent Document 4] International Publication No. WO 2006-103756        